Apolipoprotein A-I inhibits experimental colitis and colitis-propelled carcinogenesis.

In both humans with long-standing ulcerative colitis and mouse models of colitis-associated carcinogenesis (CAC), tumors develop predominantly in the distal part of the large intestine but the biological basis of this intriguing pathology remains unknown. Herein we report intrinsic differences in gene expression between proximal and distal colon in the mouse, which are augmented during dextran sodium sulfate (DSS)/azoxymethane (AOM)-induced CAC. Functional enrichment of differentially expressed genes identified discrete biological pathways operating in proximal vs distal intestine and revealed a cluster of genes involved in lipid metabolism to be associated with the disease-resistant proximal colon. Guided by this finding, we have further interrogated the expression and function of one of these genes, apolipoprotein A-I (ApoA-I), a major component of high-density lipoprotein. We show that ApoA-I is expressed at higher levels in the proximal compared with the distal part of the colon and its ablation in mice results in exaggerated DSS-induced colitis and disruption of epithelial architecture in larger areas of the large intestine. Conversely, treatment with an ApoA-I mimetic peptide ameliorated the phenotypic, histopathological and inflammatory manifestations of the disease. Genetic interference with ApoA-I levels in vivo impacted on the number, size and distribution of AOM/DSS-induced colon tumors. Mechanistically, ApoA-I was found to modulate signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB activation in response to the bacterial product lipopolysaccharide with concomitant impairment in the production of the pathogenic cytokine interleukin-6. Collectively, these data demonstrate a novel protective role for ApoA-I in colitis and CAC and unravel an unprecedented link between lipid metabolic processes and intestinal pathologies.

The effect of artificial tears on computer-assisted corneal topography in normal eyes and after penetrating keratoplasty.

PURPOSE: To examine the effect of adding artificial tears for one minute to normal eyes and eyes that have undergone keratoplasty by using computer-assisted videokeratography. METHODS: We prospectively analyzed 24 normal corneas (24 patients) chosen by random number table (reproducibility section [10 eyes], tear section [14 eyes]) as well as 14 postkeratoplasty corneas. The parametric descriptors analyzed statistically included the simulated keratometry value, surface asymmetry index, surface regularity index, power at the vertex normal, and the pupil offsets from the visual axis. Vectoral analysis was used to calculate the difference in power and axis between the simulated keratometry values before and after tear instillation. RESULTS: In normal eyes, tear instillation increased the surface asymmetry index (0.28 +/- 0.34, P = .01), changed the simulated keratometry value (0.23 diopter by 27.8 degrees), and power (0.79 +/- 0.82 diopters, P = .004) and location (0.91 +/- 0.76 mm) of the steepest point of the cornea changed. In postkeratoplasty eyes, the surface regularity index decreased (0.49 +/- 0.80, P = .04), surface asymmetry index decreased (0.37 +/- 1.03, P = .21), mean simulated keratometry value changed (1.04 diopters by 1.01 degrees), and power (0.70 +/- 2.34 diopters, P = .28) and location (1.04 +/- 1.17 mm) of the steepest point of the cornea changed. Changes were greater than the variability of the surface regularity index (0.07 +/- 0.05), surface asymmetry index (0.04 +/- 0.03), simulated keratometry value power (0.08 +/- 0.06 diopter), and axis (4.6 +/- 5 degrees). CONCLUSIONS: The addition of artificial tears to normal or regular and symmetric eyes that have undergone keratoplasty worsened symmetry and changed the power and location of the steepest point. However, the addition of artificial tears to irregular eyes that have undergone penetrating keratoplasty created a more regular and symmetric surface and significantly altered the simulated keratometry values. We recommend that corneal topography be performed before the application of artificial tears.

Calculation of intraocular lens power after radial keratotomy with computerized videokeratography.

PURPOSE: Because standard methods to determine intraocular lens power are not adequate in eyes that have had radial keratotomy, we undertook this study to evaluate the corneal power derived from computerized videokeratography for use in intraocular lens power calculations. METHODS: We examined four eyes of three patients who had radial keratotomy and who underwent phacoemulsification cataract surgery with implantation of a posterior chamber intraocular lens. We used a computerized videokeratography-derived corneal curvature value in the Holladay formula for intraocular lens calculations. We determined the ideal intraocular lens power and the keratometric value that would have led to the ideal intraocular lens power from the postoperative refraction at 6.1 +/- 1.1 months after cataract extraction. The ideal keratometric value was compared with the keratometric values derived from computerized videokeratography, standard keratometry, contact lens overrefraction, and refractions before and after radial keratotomy. RESULTS: The postoperative refraction at approximately six months averaged -0.32 +/- 0.63 diopter (range, -0.88 to +0.75 diopter) different than the aim. The mean power in ring 3, which was the closest keratometric value to the ideal, disclosed only 0.09 +/- 0.73 diopter and -0.10 +/- 0.72 diopter of deviation from the ideal keratometric and intraocular lens powers, respectively. One to two weeks after phacoemulsification cataract surgery with implantation of a posterior chamber intraocular lens, the videokeratographic differential map disclosed steepening at the wound site with variable regression by six months in all patients. CONCLUSION: Results suggest that, after radial keratotomy, using the keratometric value derived from computerized videokeratography in intraocular lens calculations is more accurate than using keratometric values measured by routine methods.

Videokeratography of keratoconus in monozygotic twins.

PURPOSE: To determine the corneal topographic appearance in a pair of monozygotic twins and family members of the twins because one of the twins had keratoconus and the other appeared normal by clinical examination. METHODS: Clinical examination and videokeratography (Topographic Modeling System, Tomey) of the patient, his monozygotic twin brother, an older brother, and his parents were performed. The I-S values (difference in the average dioptric powers of symmetrical points between the inferior and superior cornea) were calculated. RESULTS: The patient, a 28-year-old man, had clinical keratoconus confirmed with videokeratography. Clinical examination of family members including a twin brother, an older brother and both parents revealed no corneal abnormalities. Videokeratography of the clinically normal twin brother showed inferior steepening with progression over time. The I-S value of the clinically normal brother was 1.36 (right eye) (greater than 2.00 SD of normal controls), which progressed to 1.69 (right eye), 1.32 (left eye) 5 months later and to 1.87 (right eye), 1.43 diopters (D) (left eye) 14 months later. Minimal asymmetric inferior steepening was noted in an older brother who had an I-S value of 0.81 (right eye), 1.27 (left eye). The mother appeared topographically normal. CONCLUSIONS: This study lends support to the existence of subclinical keratoconus detectable by videokeratography only.

Prophylactic use of acetazolamide to prevent intraocular pressure elevation following Nd-YAG laser posterior capsulotomy.

Fifty four eyes of 54 patients undergoing Nd-YAG laser posterior capsulotomy were randomly assigned to pretreatment with either 125 mg of oral acetazolamide (group A) or placebo (group B). During the first 3 hours following capsulotomy, an intraocular pressure (IOP) rise of at least 10 mm Hg was recorded in eight of the 26 eyes of group B (30.8%) and in none of the 28 eyes of group A (p < 0.01). A rise of at least 5 mm Hg was recorded in 16/26 (61.5%) and 4/28 (14.3%) eyes respectively (p < 0.001). Three eyes of group B developed an IOP greater than 35 mm Hg. We found that pretreatment with a low dose of acetazolamide is highly effective in preventing IOP elevation following Nd-YAG laser posterior capsulotomy.

Corneal topographic changes after refitting polymethylmethacrylate contact lens wearers into rigid gas permeable materials.

Polymethylmethacrylate (PMMA) contact lenses can alter corneal shape and induce corneal warpage or distortion. The purpose of our study was to determine the effects on the corneal topography after immediate refitting of long-term PMMA contact lens wearers into rigid gas permeable (RGP) materials. Six eyes with contact lens induced corneal warpage from PMMA contact lenses were assessed using the Topographical Mapping System-1. Statistical analysis was performed for the following variables prior to and approximately 6 months after contact lens refitting: best spectacle visual acuity, manifest refraction, surface regularity index, surface asymmetry index, keratometry, and simulated keratometry. Best spectacle visual acuity improved an average of 1.8 +/- 1.0 (mean +/- SD, P < 0.05) lines of Snellen visual acuity, while refraction did not change appreciably. The surface regularity index diminished by 0.51 +/- 0.32 (P = 0.01). The surface asymmetry index improved by 0.32 +/- 0.26 (P < 0.05). There was a good correlation between keratometry and simulated keratometry, and neither changed significantly after refitting with RGP contact lenses. All general topographic patterns remained unchanged throughout the study. Immediate refitting of long-term PMMA contact lens wearers into RGP materials of similar fit allows a slightly more regular and symmetric central corneal shape, which can result in improved spectacle visual acuity. The general corneal topographic patterns of contact lens induced corneal warpage did not change or improve after refitting to RGP material.